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Biomedical subjects

I Hara

Publications and source records attributed to I Hara.

At least 19 recordsLinked to original sources

Implicating a role for immune recognition of self in tumor rejection: passive immunization against the brown locus protein.

The immune system can recognize differentiation antigens that are selectively expressed on malignant cells and their normal cell counterparts. However, it is uncertain whether immunity to differentiation antigens can effectively lead to tumor rejection. The mouse brown locus protein, gp75 or tyrosinase-related protein 1, is a melanocyte differentiation antigen expressed by melanomas and normal melanocytes. The gp75 antigen is recognized by autoantibodies and autoreactive T cells in persons with melanoma. To model autoimmunity against a melanocyte differentiation antigen, mouse antibodies against gp75 were passively transferred into tumor-bearing mice. Passive immunization with a mouse monoclonal antibody against gp75 induced protection and rejection of both subcutaneous tumors and lung metastases in syngeneic C57BL/6 mice, including established tumors. Passive immunity produced coat color alterations but only in regenerating hairs. This system provides a model for autoimmune vitiligo and shows that immune responses to melanocyte differentiation antigens can influence mouse coat color. Immune recognition of a melanocyte differentiation antigen can reject tumors, providing a basis for targeting tissue autoantigens expressed on cancer.

Animals

Rejection of mouse melanoma elicited by local secretion of interleukin-2: implicating macrophages without T cells or natural killer cells in tumor rejection.

Tumor cells transduced with cytokine genes provide a model to study host-effector mechanisms involved in tumor rejection. Local IL-2 production within a tumor site mimics a specific helper-T-cell response, bypassing an immunization phase. Growth of mouse B16F10 melanomas transduced with interleukin-2 (IL-2) in syngeneic hosts were significantly delayed. IL-2-producing B16F10 cells were super-transduced with interferon-gamma to up-regulate expression of major-histocompatibility-complex (MHC) antigens. Expression of class-I- or class-II-MHC molecules did not augment tumor rejection of IL-2-secreting tumor cells. Rejection of IL-2-transduced B16F10 cells in syngeneic mice was unaffected by depletion of CD8+ T-cell and NK1.1+ natural-killer (NK) cell populations. Tumor rejection occurred in SCID mice even after depletion of NK1.1+ cells, confirming that T cells and NK cells were not required for tumor rejection. Histologic examination of sites of tumor rejection showed inflammation, characterized by infiltrates of macrophages, occasional neutrophils, and areas of necrosis. When mice were treated systemically with macrophage-colony-stimulating factor to expand monocyte pools, tumor rejection was significantly augmented further. This study shows that in situ IL-2 production can result in tumor rejection mediated by inflammatory events, possibly involving macrophages, and mimicking a delayed-type hypersensitivity (DTH) response even in the absence of T cells and NK cells. Furthermore, tumor rejection can be enhanced by systemic administration of a cytokine to expand potential inflammatory cell populations.

Animals

Reactivity of autologous CD4+ T lymphocytes against human melanoma. Evidence for a shared melanoma antigen presented by HLA-DR15.

Reactivity of CD8+ T lymphocytes against human melanoma has been extensively characterized, but little is known about melanoma Ags recognized by CD4+ lymphocytes. We have identified CD4+ CTL that recognize shared melanoma Ag(s) expressed by autologous melanoma cells and a subset of allogeneic melanomas. The same Ag(s) was shared by autologous and positive allogeneic melanomas by cross-blocking experiments. Cytotoxicity was directed against epitopes presented by HLA-DR on target melanoma cells, and allelic typing revealed that cytotoxicity was restricted through HLA-DR15. These CD4+ T cells released IFN-gamma, IL-4, and TNF-alpha, but not IL-2, in response to HLA-DR15+ target cells. CD4+ T cells did not lyse DR15+ nonmelanoma cell types, including melanocytes or fibroblasts (induced to express HLA-DR by IFN-gamma). Thus, by cytotoxicity assays, shared Ags were only recognized on melanoma cells but not on normal melanocytes. In summary, this analysis shows that melanoma cells share an Ag that is presented by HLA-DR15.

Antibodies, Monoclonal

Masseter muscle activity and the hypoglossal nerve.

The effects of severing the hypoglossal nerve and resultant restriction of tongue movement was evaluated for its effect on masticatory jaw movement. Electromyograms of masseter muscles in the feeding rat were recorded 3 days after the nerve severing operation at 1 week intervals. Even after severing the lateral branches of the hypoglossal nerve bilaterally, active-feeding behaviour continued with mastication slightly impaired. After severing the medical branches bilaterally, feeding behaviour was rarely observed, but where eating did take place mastication was impaired with marked disturbance in the masticatory rhythm.

Animals

[Nephron sparing surgery of patients with renal cell carcinoma in a solitary kidney or bilateral renal cell carcinoma].

PURPOSE: The objective of this study is to evaluate the efficacy of nephron sparing surgery for renal cell carcinoma in patients with a solitary kidney or bilateral tumors. PATIENTS AND METHODS: From 1982 to 1994, a total of 12 patients with a solitary kidney or bilateral tumors underwent nephron sparing surgery. The survival and complications were examined. RESULTS: The patients were 11 males and 1 female. Three patients were in stage 1, 6 in stage 2, 2 in stage 3, and 1 in stage 4, and the mean tumor size was 3.4 cm (0.8-6.5). The complications were post-operative bleeding in one patient and slight transient renal dysfunction which didn't require hemodialysis in 3 patients. The local recurrence was observed in 1 patient (8.3%), metastasis in 3 (25%), no evidence of disease in 8 (66.7%), alive with cancer in 1 (8.3%), death due to cancer in 2 (16.7%), death due to other disease in 1 (8.3%), and the 5 year survival of all patients was 62.5%, that was almost the same as the result of 141 renal cell carcinoma patients treated with nephrectomy in our hospital. The disease free survival rate of the patients in stage 1 and 2 seems to be higher than in stage 3 and 4 with no significant difference (p = 0.0956). CONCLUSION: These results suggest that nephron sparing surgery for renal cell carcinoma in patients with a solitary kidney or bilateral tumors is a useful therapy.

Aged

Genomic structure of the ME491/CD63 antigen gene and functional analysis of the 5'-flanking regulatory sequences.

Genomic structure of the ME491/CD63 antigen gene and promoter activity of the 5'-flanking regulatory sequences were studied. The antigen gene consists of eight exons that span 4 kilobase-pairs. Primer extension analysis with RNA from cultured human cells identified three major transcription initiation sites. The 5'-flanking region of exon 1 has features characteristic to promoters of many house-keeping genes and growth-regulating genes. The region is highly GC rich and contains potential binding sites for transcription factors such as Sp1 and ETF, but not a TATA box. The 5'-flanking sequence exerted strong promoter activity when linked to a reporter gene. Deletion mutant analysis of the 5'-flanking sequence has strongly suggested that a potential binding site for AP-1 plays an important role in positively regulating the gene expression.

Amino Acid Sequence

Clinical and pathological evaluations of methotrexate, vinblastine, adriamycin and cisplatin chemotherapy for advanced urothelial cancers.

We have treated advanced transitional-cell carcinoma of the urothelial tract with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC) chemotherapy since July of 1985. We analyzed the effect of that chemotherapy in 26 patients with advanced urothelial cancer who were treated in our hospital and followed up. They were divided into two groups. Group 1 consisted of 15 patients with distant metastases. In all, 11 of them received M-VAC as adjuvant chemotherapy for metastatic lesions after surgical removal of the primary lesion, and the remaining 4 patients were not operable since they had very advanced-stage tumors; they received only M-VAC chemotherapy. Group 2 contained 11 patients who received M-VAC neo-adjuvant chemotherapy. In group 1, the overall response rate was 57.1% and the mean duration of response was 12.6 months. In the 11 patients who had received M-VAC as adjuvant therapy after surgical removal of the primary tumor, the mean duration of response was 14.1 months. After M-VAC chemotherapy, six patients underwent surgical resection of metastatic lesions and restaging was done pathologically in these cases. The clinical response coincided with the pathological response in all six cases. In group 2, 5 of 11 patients experienced histological downstaging of the resected bladder. M-VAC chemotherapy combined with surgical resection of residual tumors has proved to be an effective option against advanced urothelial cancer.

Adult

Cytomegalic inclusion disease presenting acute intrahepatic cholestasis.

An 83-year-old man suffering from pulmonary emphysema was admitted to our hospital because of jaundice. He was diagnosed as acute intrahepatic cholestasis but the etiology could not be determined during the treatment period. In spite of treatment, the jaundice worsened progressively without any elevation in serum transaminase, and he died of respiratory failure 58 days later. An autopsy revealed a generalized cytomegalic inclusion disease, predominantly in the biliary tracts, liver and lungs. This is a rare case of cytomegalic inclusion disease presenting acute intrahepatic cholestasis without any elevation of transaminase during the clinical course.

Acute Disease

[Occupational skin hazards in hairdressers and their etiologic factors--results of mass health examination at health centers].

From 1986 to '88, mass health examinations for skin disorders among hairdressers were performed in 4 Health Centers in Osaka Prefecture. Among 306 female hairdressers examined, the prevalence of skin lesions was 49.0%, consisting of skin lesions of hands and arms alone 22.9%, nail lesion alone 13.7%, and both 12.4%. Characteristic features of the skin lesions were dryness, roughness, thickening of epidermis, redness, hyperkeratinization, scales, desquamation, etc. In the case of nails, thinning, onycholysis, onychoschisis, pitting, transverse grooves and onychorexis were characteristic. The relationship between prevalence of skin disorders and site of lesions to history or category of work was studied. For the prevention of these skin hazards, improved chemicals, equipment, and hygienic education are necessary. Periodical health-checks including participation by a dermatologist, and health supervision should be continued with cooperation between Health Centers and beauty salons, because these businesses are principally small-size enterprises.

Adolescent

[A case of progressive systemic sclerosis complicated by crescentic glomerulonephritis and diffuse pulmonary hemorrhage].

A 38-year-old man was hospitalized for proteinuria, and pitting edema. He had noticed Raynaud's phenomenon at about age fifteen. One month prior to admission, his urine contained protein and the serum creatinine was 3.0 mg/dl. On admission, sclerodactylia, digital pitting scar of fingertips, digital bone absorption and pulmonary fibrosis were observed and a diagnosis of progressive systemic sclerosis (PSS) was made. Laboratory investigations revealed: 24-hour urine protein excretion 3 g; serum creatinine 5.6 mg/dl; creatinine clearance 13.5 ml/min; antinuclear factor strongly positive in a speckled pattern; antibodies to nRNP positive with a titer of 1: 20, 480; antibodies to DNA, Sm, SS-A, SS-B, Scl-70, centromere and Jo-1 negative; serum complement normal. A renal biopsy revealed focal and segmental necrotizing glomerulonephritis with 70% crescents but no vascular changes. Circulating antiglomerular basement membrane antibodies were negative. Immunofluorescence disclosed granular deposits of IgM and C3 in the mesangium and along the capillary walls. Treatment was begun with methylprednisolone pulse therapy. After 5 month, serum creatine and creatinine clearance were 1.9 mg/dl and 35 ml/min, respectively. A year after the discharge, he was readmitted for hemoptysis and worsening of proteinuria and microhematuria. A chest radiograph demonstrated bilateral alveolar consolidation. Serum creatinine was elevated to 3.5 mg/dl. The continuous hemoptysis resulted in a severe dyspnea associated with a rapid fall in the hemoglobin. On the fourth hospital day, the PaO2 was 41 Torr on oxygen by mask that necessitated mechanical ventilation and pulse therapy was started. However, the patient died on the ninth hospital day of respiratory failure due to pulmonary hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[A study of comparison between Technicon THMS H-2 and Hematrak 590].

Using 655 peripheral blood samples from normal individuals and patients, we evaluated the relationship between the measurements of red blood cell (RBC) and white blood cell (WBC) through the Hematrak 590 (Hematrak) and the generated flag systems in the Technicon H-2 (H-2). 1) Among the 12 VAR (Variation) flag positive samples in H-2, 10 samples were obtained from the patients receiving blood transfusions. The samples with high values of HDW (Hemoglobin distribution width) in H-2 seemed to have hypochromatic and polychromatic changes in RBC. 2) Hematrak is likely to be more sensitive than H-2 in discovering atypical lymphocytes (AL). When AL counts in Hematrak were over 5 or 6% of WBC, these results were coincident with ATYP flag positive in H-2. 3) In our examinations, when %Blast in H-2 was over 4%, BLASTS flag always generated positively. We think that H-2 is a tool with high reproducibility for the detection of the blast-like abnormal cells. 4) We evaluated the results of WBC differential count by the three methods of H-2, Hematrak and manual procedures in the peripheral blood samples from normal individuals. We recognized close correlations in neutrophils, lymphocytes and eosinophils (coefficients of correlation = 0.826-0.911), and relatively close ones in monocytes (r = 0.280-0.562), but no correlations in basophils (r = 0.106-0.281). To comprehend the pathophysiological states of the various diseases hematologically, it is necessary to understand the characteristics of the different measurement principles between the two instruments (H-2 and Hematrak).

Blood Cell Count

[Automated assay method for protein C anticoagulant activity].

We developed an automated assay method for protein C anticoagulant activity to prolong the APTT measured with automated coagulation apparatus. The automated assay method required following three reagents. One was 0.025 mol/l calcium chloride solution. The other two were a protein C deficient plasma and a phospholipid plus protein C activator both of which constituted a recomposed protein C assay kit (BMY). 0-50% activities of protein C and clotting times were regressed on normal linear curve, while 25-150% activities and clotting times were regressed on logarithmic curve. The coefficients of variation were 2.9-3.4% (intra-assay) and 3.6-3.9% (inter-assay). A correlation of protein C activities between measured by automated assay method and by ordinary manual method was good (r = 0.954). Our data suggest that this automated assay is a useful method for measuring the protein C anticoagulant activities utilizing a coagulation apparatus.

Blood Coagulation Tests

[Health effects and personal protection in pest control workers using organophosphorus insecticides].

One hundred and sixteen pest control workers (16 termite control workers (Sprayer I), 46 cockroach or fly-control workers (Sprayer II) and 56 both termite and cockroach or fly-control workers (Sprayer III)) were surveyed by a questionnaire and health examinations. Variety and quantity of pesticide used, personal usage of protective devices (respirator, gloves, work clothes, under wear), and conditions related to bathing were studied by a questionnaire. Relationships between protective devices and blood cholinesterase activity (ChE) were also analyzed. Significant findings were as follows: Most of the pest control operators wore gum gloves and gas masks when involved in termite control. However in the case of cockroach or fly-control, 38% did not wear gloves, and for respiratory protection 44% wore gas masks while 25% of them did not even use any form of respirators. In spite of having better protective practices than sprayers II and III, sprayer I showed significantly lower plasma ChE activity than both sprayer II and III. Plasma ChE activity in sprayers who put on simple respirators tended to be lower than those using gas masks. Plasma ChE activity was also significantly lower in those workers who had less frequent changes of work clothes compared to those with more frequent.

Adult

[A study on work and daily life factors affecting the health of taxi drivers].

In order to elucidate factors affecting taxi drivers health, a questionnaire survey was performed on 5523 taxi drivers and health examinations were conducted on 311 taxi drivers from among them. Analysis by a method of multivariate analysis called Quantification II was performed with dependent variables being blood pressure, the number of subjective symptoms and fatigue on rising, and independent variables being work and daily life conditions. The major results of this survey were as follows: 1) A tendency for hypertension risk to increase with degree of obesity, and both employment as a taxi driver for 1-4 years and over twenty years of taxi driving were positively associated with increase in risk for hypertension. 2) Common factors to all types of work shifts which were related to an increase in the number of subjective symptoms were irregularity of meals, insufficient rest on off days, large number of years engagement at taxi driving, frequent frightening experiences while driving and comparatively short driving distance in one shift. 3) Common factors to all types of work shifts that were connected with fatigue at the time of rising were insufficient rest on off days and long years engagement in taxi driving.

Activities of Daily Living

[Statistics on operations at Hara Genitourinary Hospital (1971-1991)].

The statistical analysis of the inpatients and operations in our department from April, 1971 to March, 1991 revealed a total of 9,170 operations. One of the biggest changes in treatment is a marked increase in closed surgery. This includes endourological surgeries; transurethral resections of prostate and bladder tumor (TUR-P, TUR-Bt), percutaneous nephrolithotripsy (PNL), transurethral uretero-lithotripsy (TUL) and extracorporeal shock-wave lithotripsy (ESWL). From 1976 to 1980 there were 721 open surgical procedures (71.0% of cases) and 295 closed procedures (21.0% of cases). This ratio has now been reversed completely. From 1986-1991, there were 342 open procedures (8.2% of cases) and 3808 closed procedures (91.8% of cases). The main reason for this change was the introduction of the new techniques PNL, TUL and ESWL. Other important observations include: The incidence of emergency operations was higher in this private institution than that seen in non-private hospitals. From 1986, there was an increase in the use of PNL and TUL for the management of urinary calculi, and from 1988, ESWL has overtaken PNL and TUL in the treatment of this condition. Recently the limitations of ESWL have been appreciated and the value of a combined approach to therapy, for selected cases, is being recognized. A total of 238 ileal or ileocecal conduits were created with good results. A low complication rate has been observed with preservation of renal function.

Female

Tumor rejection antigens on BALB3T3 cells transformed by activated oncogenes.

The clonal expression of tumor rejection Ag (TRA) was analyzed on nine different clones derived from parental BALB3T3 cells that were transfected with activated H-ras, polyoma middle T (PyMT), c-myc, and v-src oncogenes. It was shown that Bras-h clone, which is an activated H-ras oncogene-induced transformant, expressed TRA as assessed in the transplantation study using syngeneic BALB/c mice. This TRA was not detected on parental BALB3T3 nontransformed cells, suggesting that TRA could be expressed in the BALB3T3 cell transformation. Furthermore, the cross-protection experiments indicated that this TRA was also conferred on other BALB3T3 transformants with high anchorage-independent growth potential such as an activated H-ras transformant Bras-d, and PyMT transformants BMT-f, BnMT-11, BnMT-20, except in the case of one H-ras transformant Bnr-12. In contrast, this TRA was not expressed on the transfectants with little or no anchorage independent growth potential such as a PyMT transfectant BnMT-4, a c-myc transfectant Bmyc-7, and a v-src transfectant Bsrc-7. We developed the mAb BRH19 that could react with TRA+ clones but not with TRA- clones. This mAb makes an immunoprecipitate, which is composed of a 50-kDa single polypeptide chain from Bras-h cell lysate. An injection to mice with this antigen could confer the protection against Bras-h challenge. These data indicate that the 50-kDa putative TRA molecule could be expressed in close association with the cell transformation, irrespective of the introduced oncogenes, and there may exist some regulatory mechanisms rather than individually distinct manners for the expression of TRA.

3T3 Cells

Natural killer target molecules associated with the transformation of the oncogene-transfected fibroblast.

Cell surface antigens, the expression of which is highly enhanced along with the transformation of cells, were analyzed. W14 and W31, EJ-ras oncogene-induced transformants of a WKA rat fetus-derived fibroblast WFB, strongly expressed several transformation-associated antigens as defined by monoclonal antibodies 109, 061, and 081. These monoclonal antibodies recognized Mr 86,000, 62,000, and 101,000 molecules, each composed of a single polypeptide chain. The expression of these transformation-associated antigens was negligible on parental WFB cells. Transforming growth factor-beta could enhance the expression of all of these transformation-associated antigens, but platelet-derived growth factor could only enhance the Mr 86,000 kd molecule expression. In the cytotoxicity assays, poly-I:C-induced rat splenic NK cells were cytotoxic to W14 and W31, but not to WFB. The data also showed that the cytotoxicity by these NK cells against NK-sensitive YAC-1 cells was absorbed with the addition of W14, W31, platelet-derived growth factor, or transforming growth factor-beta-stimulated WFB cells. This indicates that NK cells may recognize common target antigens that are expressed among these target cells. It was also indicated that Mr 86,000 and 62,000 molecules were strongly involved in this cytotoxicity, possibly as the target antigens, since F(ab')2 fragments of monoclonal antibodies 109 and 061 strongly inhibited the cytotoxicity. The addition of monoclonal antibody 109, but not 061, inhibited the cytotoxicity even at 60 min after mixing with the effector and target cells, suggesting that the Mr 86,000 molecule may participate in the lethal hit phase of cytotoxicity by NK cells. These data may indicate that some, but not all, transformation-associated antigens are virtually important in the antitumor surveillance mechanisms by the host effector cells, such as NK cells.

Animals